Emerging role of anti-proliferative protein BTG1 and BTG2

Abstract

The B cell translocation gene 1 (BTG1) and BTG2 play a key role in a wide range of cellular activities including proliferation, apoptosis, and cell growth via modulating a variety of central biological steps such as transcription, post-transcriptional, and translation. BTG1 and BTG2 have been identified by genomic profiling of B-cell leukemia and diverse lymphoma types where both genes are commonly mutated, implying that they serve as tumor suppressors. Furthermore, a low expression level of BTG1 or BTG2 in solid tumors is frequently associated with malignant progression and poor treatment outcomes. As physiological aspects, BTG1 and BTG2 have been discovered to play a critical function in regulating quiescence in hematopoietic lineage such as Hematopoietic stem cells (HSCs) and naïve and memory T cells, highlighting their novel role in maintaining the quiescent state. Taken together, emerging evidence from the recent studies suggests that BTG1 and BTG2 play a central anti-proliferative role in various tissues and cells, indicating their potential as targets for innovative therapeutics. [BMB Reports 2022; 55(8): 380-388].

Fig. 1

Summary of human BTG/Tob protein family. (A) The schematic dia-gram shows amino acid sequence-based similarities between the BTG/Tob family members. Indicated are the total length of the proteins and simi-larity rate (percentage) of amino acids in the BTG domain (light gray) and the C-terminal region. Also, the conserved PAM2 (black) and box c domain are shown in the schematic representations. (B) Domains of BTG1 and BTG2. The APRO domain, which is conserved in BTG1 and BTG2, contains three motifs; box A, box B, and box C. These boxes make it easier for proteins to interact with one another. Box C (yellow) is found only in BTG1 and BTG2. Box A is known to interact with CNOT7/8 and nuclear receptors. Box B is known for its association with CNOT7/8. Box C is required for interacting with PRMT1 and PABPC1. The core regions of BTG1 and BTG2 in-clude two LxxLL motifs (black), which are known to enhance nuclear receptor interaction.